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Nutrition is the basic source of energy that fuels the body for everyday activities. The right kinds of food will provide a supply of all the vital nutrients that is needed to ensure the body's growth, vitality, fertility, and maintenance.
Nutrition also involves an understanding of how a healthy diet prevents the development of diseases, infections, and other conditions of the body. The study of nutrition allows for an insight of how certain illnesses and conditions may be triggered by poor diet, metabolic diseases, food allergies, and other dietary factors.Â
Nutrition is commonly seen as a combination of basic requirements such as food and water. Good nutrition involves receiving the right amounts of macronutrients and micronutrients. Macronutrients consist of carbohydrates, proteins, and fats whereas micronutrients consist of water, vitamins, and minerals. Carbohydrates supply the body with energy and help in cellular formation. The recommended intake of carbohydrates is approximately 60% of the food eaten.
Nourishment is an essential requirement to maintain health and the protection from illnesses and problems. A well nourished body willÂ ensure that the nutrients that are found in food are equally distributed to all parts of the body. A lack of nutrients leads to the regular bodily processes being affected and eventually, will lead to an increased risk to illness.
This report has focused on Glucosamine, vitamins and minerals. The report focuses on vitamin A and antioxidants and details on beta - carotene which is a provitamin A. The report also investigates the role of vitamin E as an antioxidant.
What is Glucosamine
Glucosamine, with the chemical formula of (C6H13NO5), is an amino monosaccharide. Essentially it is a sugar but has an amino group (NH2) in place of a hydroxyl group (OH).
The compound glucosamine sulphate can be derived from chitin. Chitin is the second most abundant polymer on earth and is found in crab, lobster, shrimp or oyster shells. It can also be produced by synthetically. In Europe (except the UK), glucosamine is available as a prescription medication and as a dietary supplement  in UK and North America.
Glucosamine is found in almost all human tissues but the highest concentration is found in the liver, kidney and cartilage. It is an essential building block required for the biosynthesis of various compounds including glycolipids, which are lipids that are covalently bonded to monosaccharides or polysaccharides, glycoproteins. Glycoproteins are proteins that contain oligosaccharide chains (glycans) covalently attached to polypeptide side-chains, glycosaminoglycans that are negatively charged heteropolysaccharides molecules, and proteoglycans that are formed of glycosaminoglycans (GAGs) covalently attached to the core proteins. All the compounds are intimately involved with joint structure and function.
Directly or indirectly, glucosamine plays a role in the formation of articular surfaces, tendons, ligaments, synovial fluids, skin, bone, nails, heart valves, blood vessels and mucous secretion within the digestive, respiratory and urinary systems 
Glucosamine supplements are widely used for the treatment of osteoarthritis, particularly knee osteoarthritis (OA). In osteoarthritis, cartilage, which is the rubbery material cushioning joints, becomes stiff and loses its elasticity. This makes the joint prone to damage and may lead to pain, swelling, loss of movement and further deterioration.
Since the body's natural glucosamine is used to make and repair joint cartilage, taking glucosamine as a nutritional supplement is thought to help repair damaged cartilage by augmenting the body's supply of glucosamine. 
Mechanism of glucosamine incorporation in to human tissue
Glucosamine is integrated by chondrocytes into the components of the GAG chains in unbroken cartilage, stimulating the synthesis of physiological proteolglycans. It also decreases the activity of catabolic enzymes, including matrix metalloproteases (MMP).
In certain tissues, glucosamine has a higher affinity for glucose transporters than glucose itself and is incorporated into glycoproteins faster than glucose. It also inhibits the degradation of articular cartilage induced by interleukin 1 and lipopolysaccaharides. This supports the suggestion that exogenous glucosamine acts mainly as a substrate for biosynthesis of mucopolysaccharides and biopolymers of joints and bones and, consequently, contributes to restoration of damaged cartilage. 
Articular cartilage in OA of the knee
The degenerative disease, OA, is a symptom of an imbalanced synthesis of articular cartilage (AC) surrounding substance and the associated growth factors. Knee cartilage deficiency, for example, may result in an increased rate of cartilage breakdown, leading to decreased cartilage volume and joint space narrowing. OA represents loss of homeostasis in the normal maintenance of articular cartilage by the degradation and synthesis of the matrix components. The mechanisms are not fully understood, although the aetiology seems to be controlled by many factors. The end pathway is an imbalance between proteinases, which break down the matrix constituents, and proteinase inhibitors. 
The role of glucosamine in OA of the knee
Besides synthesis of GAGs, it also exerts an anti-catabolic effect on AC by inhibiting the anti-inflammatory responses.
Transforming growth factor - beta (TGF-Î²) is considered to be small cell-signalling protein molecule that is secreted by the glial cells of the nervous system and by numerous cells of the immune system. These are a category of signalling molecules used extensively in intercellular communication, known as a cytokine. They play key roles in many downstream effects, such as mesenchymal differentiation, matrix production, stimulation of chondrocytes and controlled differentiation of stem cells. Some cells secrete TGF-Î², and also have receptors for TGF-Î², this is known as autocrine signalling. Cancerous cells increase their production of TGF-Î², which also acts on surrounding cells. TGF-Î² exists in three isoforms called TGF-Î²1, TGF-Î²2 and TGF-Î²3.
The peptide structures of the three members of the TGF-Î² family are highly similar. They are all encoded as large protein precursors, TGF-Î²1 contains 390 amino acids and TGF-Î²2 and TGF-Î²3 each containing 412 amino acids. They each have an N-terminal signal peptide of 20-30 amino acids that they require for secretion from a cell, a pro-region called latency associated peptide (LAP), and a 112-114 amino acid C-terminal region that becomes the mature TGF-Î² molecule following its release from the pro-region by proteolytic cleavage.  The mature TGF-Î² protein dimerizes to produce a 25 KDa active molecule with many conserved structural motifs.  TGF-Î² has nine cysteine residues that are conserved among its family, eight form disulfide bonds within the molecule to create a cysteine knot structure characteristic of the TGF-Î² super family. The ninth cysteine forms a bond with the ninth cysteine of another TGF-Î² molecule to produce the dimer.  Many other conserved residues in TGF-Î² are thought to form secondary structure through hydrophobic interactions. The region between the fifth and sixth conserved cysteines houses the most divergent area of TGF-Î² molecules that is exposed at the surface of the molecule and is implicated in receptor binding and specificity of TGF-Î².
In adults, TGF-Î²'s are also believed to maintain a critical balance between the various anabolic and catabolic functions of chondrocytes for proper functioning of the cartilage. There is also evidence that glucosamine mediates the increase in the production of specific matrix components involved in TGF-Î²1 up-regulation, possibly through the hexosamine pathway in optimal concentrations of glucosamine. The effect of glucosamine on chondrocytes was found to be dependent on the culture conditions. There is an effect on gene expression, in both anabolic and catabolic activities of chondrocytes, in response to glucosamine treatment in the human OA explant model. Another study added a pre-culture experimental agent to human cartilage harvested during knee arthroplasty procedures. To this model, they added different concentration of glucosamine and they found that glucosamine (5Â mM) addition to a human OA explant reduced the enzymatic breakdown of the cellular matrix. 
The authors of this study also suggested that chondroprotective properties of the glucosamine in vivo may be based on inhibiting further degradation due to catabolic activities, rather than on the ability to rebuild cartilage.
Vitamins are essential for bodily functions and overall well being and needed by the body in small amounts. Generally, people who eat a healthy, balanced diet do not need vitamin supplements as this is provided from their diet. Some people may benefit from taking supplements. These people include elderly people, people with chronic illness or recovering from an illness or injury, pregnant women and people who do not eat a balanced nutritious diet. 
Each vitamin has its own role within the body. For example Vitamin D which is a fat soluble vitamin (discussed below) plays a role in the absorption of calcium, which is essential for the maintenance of healthy bones. Where Vitamin C, a water soluble vitamin (discussed below), plays a role in stimulation of certain enzymes, collagen biosynthesis, hormonal activation, antioxidant, detoxification of histamine, phagocytic functions of leukocytes, formation of nitrosamine and proline hydroxylation amongst others  .The body is unable to manufacture vitamins itself. Vitamins can be divided into fat-soluble and water soluble.
Water soluble vitamins dissolve in water and are not stored by the body. Excess amounts are removed in urine therefore must be replaced every day in our diet to provide a continuous supply.
Water soluble vitamins are easily ruined or washed away during food storage and preparation, but following accurate actions in these two areas can reduce this loss. It's best to refrigerate fresh produce, keep milk and grains away from strong light, and use the cooking water from vegetables to prepare gravy or soups. Water soluble vitamins include B vitamins and folic acid. Usually; water-soluble vitamins are not harmful as the body excretes excess levels in urine.
Fat soluble vitamins are found mainly in fatty foods such as animal fats, dairy foods, vegetable oils, liver and oily fish. As they are fat soluble, the body can store any excess in the liver and fatty tissue. If excess is consumed and then stored, through food or vitamin supplements it can be harmful. Fat soluble vitamins include Vitamin A, D, E and K.
Vitamin A are grouped compounds that play an important role in vision, bone growth, reproduction, cell division, and cell differentiation where a cell becomes part of the brain, muscle, lungs, blood, or other specialized tissue.  Vitamin A helps regulate the immune system, by making white blood cells that destroy harmful bacteria and viruses, this helps prevent or fight off infections. 
Vitamin A promotes healthy surface linings of the eyes and the respiratory, urinary and intestinal tracts. It becomes easier for the bacteria to cause infection when these linings break down. Vitamin A also helps the skin and mucous membranes function as a barrier to bacteria and viruses.
In general there are two categories of vitamin A, depending on whether the food source is an animal or a plant.
Vitamin A found in foods that come from animals is called preformed vitamin A. It is absorbed in the form of retinol, which is one of the most practical forms of vitamin A. Sources includes liver, whole milk, and some fortified food products. Retinol can be made into retinal and retinoic acid in the body. 
Vitamin A that is found in brightly coloured fruits and vegetables is called provitamin A carotenoid and retinol is its active metabolites. The term retinoid is used to include retinol and its derivatives and analogues, either naturally or occurring or synthetic.  The main biological active retinoids are:
Common provitamin A carotenoids beta - carotene, alpha- carotene, beta cryptoxanthin. Beta-carotene is the one that is most ably made into retinol. Alpha-carotene and beta-cryptoxanthin are also converted to vitamin A, but only half as efficient as-beta-carotene.
There are 563 other identified carotenoids, less than 10% can be made into vitamin A in the body.  Lycopene, lutein, and zeaxanthin are carotenoids, but do don't have vitamin A action. The Institute of Medicine (IOM) encourages consumption of all carotenoid rich fruits and vegetables for their health-promoting benefits.
Some provitamin A carotenoids function as antioxidants in the laboratories; though, this role has not always been demonstrated in humans. Antioxidants protect cells from free radicals, which are potentially damaging by-products of oxygen metabolism that may contribute to the development of some chronic diseases. 
Metabolism of Vitamin A
Together with membrane- bound cellular lipid and fat-containing storage cells, preformed vitamin A in animal cells arises as retinyl esters of fatty acids. In addition foods of vegetable origin provitamin A carotenoids are also associated with cellular lipids, but are implanted in complex cellular structures. Normal digestive processes free vitamin A and carotenoids from surrounding foods. This process is more efficient from animal tissures than from vegetable tissues. Retinyl esters are hydrolysed and the retinol and the freed carotenoids are integrated into lipid-containing micellar solutions. Fatty acids, monoglycerides, cholesterol and phospholipids, which are all products of fat digestion and secretions in the bile, are vital for retinol and lipophillic carotenoids to be more soluble in the aqueous intestinal surrounding. The micellar solubilisation is important so that they can pass easily into the lipid - rich membrane on intestinal mucosal cells. Diets low in dietary fat or diseased conditions that hinder the normal digestion and absorption of retinol and carotenoids leads to steatorrhoea, this is the presence of excess fat in the faeces due to excess lipids. Retinol and several carotenoids enter the intestinal mucosal brush border by diffusion with the concentration gradient between the micelle and plasma membrane of intestinal absorptive cells (enterocytes). Some carotenoids pass into the enterocytes and are made soluble into chylomicrons without an additional change, and some of the provitamin A carotenoids are converted into retinol. Retinol is trapped intracellularly by binding to specific binding intracellular proteins or by re-esterfication. Unconverted carotenoids, retinyl esters and the other lipids are integrated into chylomicrons and are taken out as body waste into the intestinal lymphatic channels. Then through the thoracic duct it is then delivered to the blood.
From circulating chylomicrons, tissues remove some of the carotenoids and most of the lipids. However, the retinyl esters are firstly exposed by the chylomicrons remnant, they are then hydrolysed and taken up by a group of liver cells. If the retinol is not needed immediately it is re-esterfied and reserved in the stellate cells in the liver. Most of the body's reserved vitamin A is left in the liver and the carotenoids are left in the fatty tissues throughout the body. The synthesis of carotenoids in tissues are relatively slow, but when an individual has a low dietary intake of carotenoids, the reserved carotenoids are used.
After the hydrolysis of the stored retinyl esters, retinol combines with retinol binding protein (RBP), this occurs in the liver cells but may also take place in some peripheral tissues. The RBP - retinol complex is secreted into the blood and links with transthyretin which is a large protein. This together with the RBP - retinol complex makes a transthyretin - RBP - retinol complex. This complex circulates in the blood delivering the lipophillic retinol to tissues and due to its large size it is not lost through kidney filtration.
The RBP - retinol complex links with target tissue membranes and intracellular binding proteins and extract the retinol. Some of the rapid isolated retinol is released into the blood unchanged and is recycled. A restricted reserve of intracellular retinyl esters is created that later provides active retinol as it is needed intracellularly. These are isomers of retinoic acid. During metabolism, active forms of vitamin A are linked to particular cellular proteins bound with retinoids with in cells and mediate retinoid action on the genome with nuclear receptors. Retinoids change the transcription of several hundred genes.
RBP - retinol complex is filtered in to the glomerulus but is recovered from the kidney tubule and recycled. Vitamin A normally leaves the body through urine as inactive metabolites.
Below is a schematic diagram of the metabolism of Vitamin A. It shows the digestion, absorption and initial handling of dietary Vitamin A.
E:\Final year\Lit project\vitamin A metabolism.bmp
The Recommended Daily Amount (RDA) is the amount of a particular vitamin or mineral that is needed each day by the average healthy person to prevent deficiency. For Vitamin A the RDA is 800Âµg. No more than 800Âµg daily, and if a lot of liver or liver products are consumed this should be a lot less. 
Essential vitamins are needed by the body for lots of different bodily functions, such as clotting of the blood, normal growth, eyesight and digestion. If a person does not get a sufficient amount of an essential nutrient they will gradually start to show deficiency symptoms. Vitamin A deficiency (VAD) is not easily defined, but the World Health Organisation (WHO) define it as tissue concentrations of vitamin A low enough to have poor health consequences even if there is no evidence of clinical xerophthalmia. Xerophthalmia is a medical condition when the eye fails to produce tears. VAD can cause irreversible blindness, an increase in morbidity and death, a poor reproductive health, an increased risk of anaemia and can also contribute to slow growth and development. However, these can also be caused by other nutritional deficiencies. VAD is most common in developing countries like Africa, Asia and Western Pacific. It is rare in the UK. Vitamin A deficiency is the single greatest preventable cause of childhood blindness. People most at risk are children between six months to six years, pregnant women, and lactating women. In pregnant women VAD causes night blindness and may increase the risk of maternal mortality.
19Vitamin A can cause side effects when taken in excessive amounts. Most causes of vitamin A toxicity are due to accidental ingestion of doses exceeding 200,000 Âµg. Adverse reactions to acute ingestion are usually temporary and include loss of appetite, irritability, fatigue, weakness and vomiting. Chronic vitamin A toxicity may occur following many months of daily intake of the vitamin in amounts exceeding 4200 Âµg in children and 7500 Âµg in adults, and is most likely to develop in individuals taking high doses of vitamin A compounds to treat skin disorders, or in those with poor liver function.
The symptoms of chronic toxicity in infants include growth retardation of the long bones (for example, the femur bone in the leg) and premature epiphyseal bone closing. In adults, vitamin A toxicity causes a variety of health conditions, including dry and itchy skin, dry and brittle fingernails, hair loss, headaches, visual changes, bone and muscle pain, fatigue, irritability, depression, fever, liver damage, anaemia and/or loss of appetite. In most cases, these illnesses begin to disappear as soon as vitamin A intake is decreased.
Vitamin A can also act as an antioxidant and this will be considered in the section below named antioxidants.
Antioxidants are substances or nutrients in our foods which can prevent or slow the oxidative damage to our body. When our body cells use oxygen, they naturally produce free radicals which can cause damage. Antioxidants act as free radical scavengers and therefore prevent and repair damage done by free radicals. Â Free radicals are unstable chemicals formed in the body during metabolism and from exposure to environmental sources such as pollution and cigarette smoke. Free radicals are necessary for energy metabolism and immune function, but when an excessive number of free radicals are formed, they can attack healthy cells  .
A free radical is a molecule that contains an unpaired electron, they are unstable due to its aromatic or molecular structure and they are also reactive as they are unstable. They are produced continuously in cells whether it be accidental by products of metabolism or deliberately. Examples of free radicals include superoxide (O2â€¢ -), nitric oxide (NOâ€¢) and hydrogen peroxide (H2O2).
There are three steps to free-radical chain reaction: initiation, propagation, and termination. In the initiation step, free radicals are formed from molecules that readily give up electrons, such as hydrogen peroxide. In the propagation steps, the chain-carrying radicals are alternately consumed and produced. In the termination steps, radicals are destroyed. Thus, without termination by an agent such as an antioxidant, a single free radical can damage numerous molecules, including DNA. Free radical damage has a systemic effect on the whole body.
Members of the Food and Nutrition Board of the National Research Council in the US defines a dietary antioxidant as a substance in foods which significantly decreases the adverse effects of reactive oxygen species, reactive nitrogen species or both on normal physiological functions in humans  . However this definition can be doubtful as maintenance of membrane stability is also a feature of antioxidant function  and both vitamin A and zinc are an important antioxidant function.
As mentioned in the previous section, vitamin A is found in colourful fruits and vegetables and are called provitamin A carotenoid. An example of provitamin A carotenoids beta- carotene. Fruits and vegetables are good sources of antioxidants and diets rich in these are associated with lower risk of the chronic diseases of cancer and heart disease  .
The antioxidant properties of the carotenoids depend on the oxygen tension (partial pressure) and concentration  . At low oxygen tension beta- carotene acts as a chain breaking antioxidant, whereas at high oxygen tension it readily auto-oxidises shows pro-oxidant behaviour  . Evidence suggests that beta-carotene has antioxidant activity between 2 and 20 mmHg of oxygen tension, but at the oxygen tension in air or greater than 150 mmHg it is less effective as an antioxidant.
Beta- carotene is the main source of provitamin A in the diet. Approximately 2-6 mg of beta-carotene is consumed by adults daily in developed countries  . Beta-carotene has two six- membered carbon rings which are also called beta-ionone rings separated by 18 carbon atoms in the form of a conjugated chain of double bonds. Beta-carotene is distinctive in having two beta-ionone rings in its structure, both are needed for the activity of vitamin A. The antioxidant properties of the carotenoids, the system of conjugated double bonds that occupies the central part of the molecule and various functional groups of the terminal ring structure are very much connected  . Carotenoids are efficient at suppressing singlet oxygen. In this process the carotenoids absorbs the excess energy from singlet oxygen and then releases it as heat. Carotenoids are important for protecting plant tissues as the singlet oxygen is generated during photosynthesis. Beta- carotene has been used in the treatment of erythropoietic protoporphyria this is a rare disorder passed down through families, where part of the haemoglobin called heme is not made properly  . Some research shows also shows that large amounts of dietary carotenes may provide protection against solar radiation but the research for this is unclear.
Vitamin E has eight naturally occurring forms that are found in plants. They include four tocopherols (alpha, beta, gamma and delta) and four tocotrienols (alpha, beta, gamma and delta). These are shown below. The structure that is common to all forms of vitamin E consists of a chromanol ring where 16 hydrophobic carbon tail are attached. The alpha, beta, gamma and deltaforms of tocopherol differ in the position and number of methyl groups on the chromanol ring. The only structural difference between the four types of tocotrienols is the presence of three double bonds in the tail.
There are three asymmetric centres on the tocopherols or tocotrienols molecule that give rise to stereo isomers. These are C2 on the chromanol ring and C4' and C8' on the tail. Therefore there are eight theoretical stereoisomers for each of the vitamin E compounds.
Antioxidant function of vitamin E
29Vitamin E is a powerful antioxidant and plays an essential role in protecting the cell membranes and plasma lipoproteins from free radical damage. The free radicals contain an unpaired electron and reacts readily with polyunsaturated fatty acids, proteins, carbohydrates and DNA. Vitamin E is able to neutralise free radicals because the hydroxyl group on the chromanol ring readily gives up and electron or hydride group to the free radical. Through this oxidative reaction, the unpaired electron in the free radical becomes paired and therefore less reactive. However, they hydroxyl group on the vitamin E now has an unpaired electron. This results in a vitamin E radical (Vit Eâ€¢) and can react with another free radical and be permanently inactivated to stable the vitamin E quinone (vit E=O) or it can be regenerated to active vitamin E (Vit E-OH) by reacting with vitamin C or glutathione. Fatty acids that are polyunsaturated are abundant in all cell membranes have an important influence on membrane fluidity and function. However, their double bonds make them vulnerable to oxidation by free radicals. Fortunately, most vitamin E in the body is found in cell membranes where its function is to protect polyunsaturated fatty acids from free radical attack. If a fatty acid radical is produced, vitamin E stabilises the free radical and prevents it from reacting with the neighbouring polyunsaturated fatty acids and spreading the reaction along the membrane with terrible consequences.
The recommended daily amount (RDA) for vitamin E is 10mg, this helps with good skin and immune system. As an antioxidant it protects against cell damage and helps with DNA repair.
The aim of this report was to investigate do food supplements play a role in nutrition. This report investigated the metabolism of glucosamine in the knee and its role in OA. After extensive research it was found that glucosamine acted as a placebo.
Throughout the course of this report the metabolism of vitamin A and E as antioxidants were investigated. This provided a further insight to how vitamin A is used in aiding the immune system to fight infections. Whereas vitamin E aids in the protection of the cell membrane and plasma lipoproteins from free radical damage.
There are toxicological effects to all the supplements mentioned in the report. Glucosamine taken excessively can cause gastric fluctuations such as soft stools, diarrhoea or nausea. Excessive Vitamin A can cause various toxic effects as mentioned in depth in the vitamin part of the report, however these effects will disappear once the intake of vitamin A taken is reduced. Whereas vitamin E toxicological effects can be seen without any apparent harm, occasionally muscle weakness, fatigue, nausea, and diarrhoea occur. The most significant risk is bleeding. However, bleeding is uncommon unless the dose is more than 1000 mg/day or the patient takes oral Coumarin or Warfarin
Therefore it can be stated that the objective of this report has been achieved successfully.
In conclusion proper nutrients and vitamin supplements build a strong immune system and thus result in fewer illnesses.